Multicentric, open label, pragmatic, randomized, controlled trial to compare the clinical outcome with 0.5 versus 1.0 mg entecavir for hepatitis B related decompensated cirrhosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 390
- 试验地点
- 5
- 主要终点
- Compare the proportion of participants achieveing a ‘composite primary end point’ (further decompensation or hepatocellular carcinoma or liver related death) in 12 months of follow-up.
研究概览
简要总结
Chronic HBV infection is treated with 0.5 mg entecavir once daily. However, those with decompensated cirrhosis are treated with 1.0 mg entecavir daily. There is no justification or literature to support 1.0 mg entecavir in treatment naïve decompensated cirrhosis. Our hypothesis is that the entecavir use in a higher dose of 1.0 mg in unlikely to improve the clinical outcomes. In our pilot study, we compared the viral suppression achieved with 0.5 mg versus 1.0 mg doses of entecavir in treatment naïve HBV decompensated cirrhosis and showed that the higher dose of entecavir did not hasten the viral suppression. Our study had limitations of nonrandomized study design, small sample size, short follow up of 24 weeks, and failure to include clinically relevant outcomes. In our proposed multicentric, pragmatic, randomized, controlled, non-inferiority trial of 390 adult participants with HBV related decompensated cirrhosis, will randomize them in 0.5 or 1.0 mg arms, and follow for 12 months to study the following outcomes. Primary objective is to compare the proportion of participants who reach a composite primary end point further decompensation as defined by EASL or hepatocellular carcinoma or liver related death. Secondary outcomes are to compare the proportion of viremic participants who could achieve complete viral suppression, mean reduction in HBV DNA level at various time point during 12 months of treatment, and proportion of HBeAg positive participants who could lose HBeAg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 19.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •HBsAg positive
- •hemodynamic stable
- •liver cirrhosis
- •presenting with first decompensation or Child-Tutcott-Pugh (CTP) score seven or more
- •either treatment naïve or had used antivirals for less than 3 months duration
- •had detectable HBV DNA (over 50 IU/mL) at the time of start of antiviral.
- •Cirrhosis will be diagnosed with a combination of evidences on clinical, biochemical, radiological, and endoscopic examination.
- •First decompensation of cirrhosis will be defined according to the most recent definition given by BAVENO VII consensus guideline.
- •It defines first decompensation by occurrence of either overt ascites (or pleural effusion) with increased serum ascites albumin gradient [over 1.1 g/dl], or overt hepatic encephalopathy (West Haven grade II or more) or variceal bleeding.
排除标准
- •prior use of antivirals for >3 months b.
- •suspected or confirmed hepatocellular carcinoma c.
- •hepatitis C virus viremia d.
- •HIV coinfection e.
- •active alcohol intake (>30 g for men and 20 g for women daily) f.
- •concomitant hepatobiliary disease g.
- •use of immunosuppressive medication, regardless of dose, indication, and drug h.
- •present or prior malignancy, regardless of its site, nature, and stage i.
- •pre-existing chronic kidney disease, regardless of its etiology, with eGFR <50 ml j.
- •Hepatorenal syndrome k.
- •acute on chronic liver failure.
结局指标
主要结局
Compare the proportion of participants achieveing a ‘composite primary end point’ (further decompensation or hepatocellular carcinoma or liver related death) in 12 months of follow-up.
时间窗: 12 months from the time of start of entecavir after inclusion in our study
次要结局
- Compare the proportion of participants who could achieve complete viral suppression (HBV DNA 50 IU/mL)(12 months from the time of start of entecavir after inclusion in our study)
- Compare the mean reduction in HBV DNA level(at 3, 6, 9, & 12 months from the time of start of entecavir after inclusion in our study)
- Proportion of HBeAg positive participants who could seroconvert to HBeAg negative status(12 months from the time of start of entecavir after inclusion in our study)
研究者
Amit Goel
Sanjay Gandhi Postgraduate Institute of Medical Sciences